オピオイドペプチドとアドレネルゲン受容体のシグナル伝達との"クロス・トーク"は,孤立したネズミの心臓におけるシグナル伝達である
1Laboratory of Cardiovascular Science, Gerontology Research Center, National Institute on Aging, Baltimore, Md 21224, USA.
Circulation
|April 15, 1997
まとめ
オピオイドペプチド受容体 (OPRs) は,心臓のβ-アドレナリン受容体 (β-ARs) と相互作用する. デルタ-OPR刺激は,PTX感受性G""i/o"タンパク質によって媒介されるcAMPを減少させることでβ1-AR効果を抑制する.
科学分野:
- 心血管生理学 心血管の生理学
- 分子薬理学 分子薬理学
- 神経心臓病学 神経心臓病学
背景:
- 心臓細胞は,カテキオラミンとオピオイドペプチド受容体 (OPR) を両方持っています.
- オピオイドペプチドは,カテキオラミンと共に,心臓神経端末から放出される.
- ベータアドレネルゲン受容体 (β-AR) の刺激効果に対するOPRの影響を調査することは極めて重要です.
研究 の 目的:
- OPR刺激が孤立したネズミの心臓におけるβ-AR刺激に影響するかどうかを判断する.
- 相互作用のメカニズムを明らかにし,ベータ-ARサブタイプとcAMP調節に焦点を当てます.
- このクロストークにおけるG (i/o) タンパク質の役割を探求する.
主な方法:
- 孤立した,同体積のラットハートモデル.
- ノルエピネフリン (NE),ルシン・エンケファリン (LE,デルタ-OPRアゴニスト) とフォルスコリンによる刺激.
- 左心室内静脈圧 (LVSP) とcAMPレベルの測定.
- OPRアンタゴニストのナロキソンと pertussis毒素 (PTX) のメカニズム研究への使用.
- ベータ2-ARアゴニスト (ジンテロール) の効果の評価.
主要な成果:
- ノルエピネフリン (NE) は,LVSPとcAMPを増加させた.
- レウシン・エンケファリン (LE) 抑制によるNE誘発によるLVSPとcAMPの上昇.
- LEの効果はナロキソンによって逆転し,OPRの関与を示しました.
- LEは,β2-ARアゴニストによって媒介される,cAMP独立のイノトロプ反応に影響しませんでした.
- 百日咳毒素 (PTX) の前治療により,LEの抑制効果がなくなり,Gのタンパク質が関与しました.
結論:
- デルタ-OPRとβ1-ARシグナル伝達経路の間には,強力な,阻害的なクロストークが存在します.
- この相互作用は,PTX 感受性G タンパク質によって媒介されます.
- このメカニズムはアデニリルサイクラースを阻害し,ネズミの心臓のcAMPレベルを低下させます.
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